Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice

Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow rec...

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Main Authors: Ting Bei, Xusong Cao, Yun Liu, Jinmei Li, Haihua Luo, Lin Huang, Tian Tian, Lei Li, Yong Jiang
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/11/3395
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author Ting Bei
Xusong Cao
Yun Liu
Jinmei Li
Haihua Luo
Lin Huang
Tian Tian
Lei Li
Yong Jiang
author_facet Ting Bei
Xusong Cao
Yun Liu
Jinmei Li
Haihua Luo
Lin Huang
Tian Tian
Lei Li
Yong Jiang
author_sort Ting Bei
collection DOAJ
description Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.
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spelling doaj.art-dd4a46fff8f84a4f87a5aa88dc2b63792023-11-21T22:44:10ZengMDPI AGMolecules1420-30492021-06-012611339510.3390/molecules26113395Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated MiceTing Bei0Xusong Cao1Yun Liu2Jinmei Li3Haihua Luo4Lin Huang5Tian Tian6Lei Li7Yong Jiang8Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaTotal body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.https://www.mdpi.com/1420-3049/26/11/3395cells penetrating peptidesbone marrow transplantationreactive oxygen speciesengraftmentsuperoxide dismutase
spellingShingle Ting Bei
Xusong Cao
Yun Liu
Jinmei Li
Haihua Luo
Lin Huang
Tian Tian
Lei Li
Yong Jiang
Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
Molecules
cells penetrating peptides
bone marrow transplantation
reactive oxygen species
engraftment
superoxide dismutase
title Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
title_full Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
title_fullStr Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
title_full_unstemmed Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
title_short Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice
title_sort antioxidant fusion protein sod1 tat increases the engraftment efficiency of total bone marrow cells in irradiated mice
topic cells penetrating peptides
bone marrow transplantation
reactive oxygen species
engraftment
superoxide dismutase
url https://www.mdpi.com/1420-3049/26/11/3395
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AT xusongcao antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT yunliu antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT jinmeili antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT haihualuo antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT linhuang antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT tiantian antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT leili antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice
AT yongjiang antioxidantfusionproteinsod1tatincreasestheengraftmentefficiencyoftotalbonemarrowcellsinirradiatedmice